4 results on '"Fazzi, Gregorio E."'
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2. Association between mutational subgroups, Warburg‐subtypes, and survival in patients with colorectal cancer.
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Offermans, Kelly, Jenniskens, Josien C. A., Simons, Colinda C. J. M., Samarska, Iryna, Fazzi, Gregorio E., van der Meer, Jaleesa R. M., Smits, Kim M., Schouten, Leo J., Weijenberg, Matty P., Grabsch, Heike I., and van den Brandt, Piet A.
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COLORECTAL cancer ,OVERALL survival ,CANCER patients ,SOMATIC mutation ,BRAF genes - Abstract
Background: Previous research suggests that Warburg‐subtypes are related to potentially important survival differences in colorectal cancer (CRC) patients. In the present study, we investigated whether mutational subgroups based on somatic mutations in RAS, BRAF, PIK3CA, and MET, which are known to promote the Warburg‐effect, as well as mismatch repair (MMR) status, hold prognostic value in CRC. In addition, we investigated whether Warburg‐subtypes provide additional prognostic information, independent of known prognostic factors like TNM stage. Methods: CRC patients (n = 2344) from the prospective Netherlands Cohort Study (NLCS) were classified into eight mutually exclusive mutational subgroups, based on observed mutations in RAS, BRAF, PIK3CA, and MET, and MMR status: All‐wild‐type + MMRproficient, KRASmut + MMRproficient, KRASmut + PIK3CAmut + MMRproficient, PIK3CAmut + MMRproficient, BRAFmut + MMRproficient, BRAFmut + MMRdeficient, other + MMRproficient, and other + MMRdeficient. Kaplan–Meier curves and Cox regression models were used to investigate associations between mutational subgroups and survival, as well as associations between our previously established Warburg‐subtypes and survival within these mutational subgroups. Results: Compared to patients with all‐wild‐type + MMRproficient CRC, patients with KRASmut + MMRproficient, KRASmut + PIK3CAmut + MMRproficient, BRAFmut + MMRproficient, or other + MMRproficient CRC had a statistically significant worse survival (HRCRC‐specific ranged from 1.29 to 1.88). In contrast, patients with other + MMRdeficient CRC had the most favorable survival (HRCRC‐specific 0.48). No statistically significant survival differences were observed for the Warburg‐subtypes within mutational subgroups. Conclusion: Our results highlight the prognostic potential of mutational subgroups in CRC. Warburg‐subtypes did not provide additional prognostic information within these mutational subgroups. Future larger‐scale prospective studies are necessary to validate our findings and to examine the potential clinical utility of CRC subtyping based on mutational subgroups. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Expression of proteins associated with the Warburg‐effect and survival in colorectal cancer.
- Author
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Offermans, Kelly, Jenniskens, Josien CA, Simons, Colinda CJM, Samarska, Iryna, Fazzi, Gregorio E, Smits, Kim M, Schouten, Leo J, Weijenberg, Matty P, Grabsch, Heike I, and van den Brandt, Piet A
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PROTEIN expression ,COLORECTAL cancer ,RECTAL cancer ,OVERALL survival ,PROGNOSIS - Abstract
Previous research has suggested that the expression of proteins related to the Warburg effect may have prognostic value in colorectal cancer (CRC), but results remain inconsistent. Our objective was to investigate the relationship between Warburg‐subtypes and patient survival in a large population‐based series of CRC patients. In the present study, we investigated the expression of six proteins related to the Warburg effect (LDHA, GLUT1, MCT4, PKM2, p53, PTEN) by immunohistochemistry on tissue microarrays (TMAs) from 2,399 incident CRC patients from the prospective Netherlands Cohort Study. Expression levels of the six proteins were combined into a pathway‐based sum‐score and patients were categorised into three Warburg‐subtypes (low/moderate/high). The associations between Warburg‐subtypes and CRC‐specific and overall survival were investigated using Kaplan–Meier curves and Cox regression models. CRC patients were classified as Warburg‐low (n = 695, 29.0%), Warburg‐moderate (n = 858, 35.8%) or Warburg‐high (n = 841, 35.1%). Patients with Warburg‐high CRC had the poorest CRC‐specific [hazard ratio (HR) 1.17; 95% CI 1.00–1.38] and overall survival (HR 1.19; 95% CI 1.05–1.35), independent of known prognostic factors. In stratified analyses, this was particularly true for patients with tumour‐node‐metastasis (TNM) stage III CRC (HRCRC‐specific 1.45; 95% CI 1.10–1.92 and HRoverall 1.47; 95% CI 1.15–1.87), and cancers located in the rectum (HRoverall 1.56; 95% CI 1.15–2.13). To our knowledge, this is the first study to identify the prognostic value of immunohistochemistry‐based Warburg‐subtypes in CRC. Our data suggest that Warburg‐subtypes are related to potentially important differences in CRC survival. Further research is required to validate our findings and to investigate the potential clinical utility of these Warburg‐subtypes in CRC. [ABSTRACT FROM AUTHOR]
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- 2022
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- View/download PDF
4. Impaired autonomic regulation of resistance arteries in mice with low vascular endothelial growth factor or upon vascular endothelial growth factor trap delivery
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Jody J. Haigh, Patrik Verstreken, Ger M.J. Janssen, Diether Lambrechts, Peter Carmeliet, Paul M. H. Schiffers, Greet Vanhoutte, Massimiliano Mazzone, Carmen Ruiz de Almodovar, Hermann Rohrer, Jo G. R. De Mey, Gregorio E. Fazzi, Koen Poesen, Stefan Vinckier, Merlijn J. Meens, Annemie Van der Linden, Serena Zacchigna, Katarzyna Miskiewicz, Erik Storkebaum, Promovendi CD, Ondersteunend personeel CD, Farmacologie & Toxicologie, Bedrijfsbureau CD, RS: CARIM School for Cardiovascular Diseases, Storkebaum, Erik, Ruiz De Almodovar, Carmen, Meens, Merlijn, Zacchigna, Serena, Mazzone, Massimiliano, Vanhoutte, Greet, Vinckier, Stefan, Miskiewicz, Katarzyna, Poesen, Koen, Lambrechts, Diether, Janssen, Ger M. J., Fazzi, Gregorio E., Verstreken, Patrik, Haigh, Jody, Schiffers, Paul M., Rohrer, Hermann, Van Der Linden, Annemie, De Mey, Jo G. R., and Carmeliet, Peter
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Vascular Endothelial Growth Factor A ,SYMPATHETIC-NERVOUS-SYSTEM ,Vascular smooth muscle ,muscle ,SMOOTH-MUSCLE-CELLS ,Gene Expression ,Transgenic ,Muscle, Smooth, Vascular ,Neuroeffector junction ,arteries ,chemistry.chemical_compound ,Mesenteric Arterie ,Mice ,Cardiovascular Disease ,vasoconstriction ,vascular endothelial growth factor ,Medicine (all) ,nervous system ,Gene Transfer Techniques ,arterie ,Autonomic Nervous System Disease ,MESENTERIC-ARTERIES ,VEGF ,Common ,Mesenteric Arteries ,Vascular endothelial growth factor B ,Vascular endothelial growth factor ,Vascular endothelial growth factor A ,DIFFERENTIATION ,medicine.anatomical_structure ,Lac Operon ,Cardiovascular Diseases ,SURVIVAL ,Smooth ,Cardiology and Cardiovascular Medicine ,smooth ,Signal Transduction ,EXPRESSION ,medicine.medical_specialty ,Neuroeffector ,Carotid Artery, Common ,Mice, Transgenic ,RATS ,Internal medicine ,Vascular ,Physiology (medical) ,muscle, smooth ,medicine ,Animals ,Autonomic Nervous System Diseases ,Vascular Endothelial Growth Factor Receptor-1 ,Vascular Endothelial Growth Factor Receptor-2 ,Vascular Resistance ,Vasoconstriction ,ERYTHRODYSESTHESIA ,RECEPTOR ,business.industry ,Animal ,Biology and Life Sciences ,Kinase insert domain receptor ,Gene Transfer Technique ,Endocrinology ,chemistry ,Vascular resistance ,Human medicine ,Carotid Artery ,business - Abstract
Background— Control of peripheral resistance arteries by autonomic nerves is essential for the regulation of blood flow. The signals responsible for the maintenance of vascular neuroeffector mechanisms in the adult, however, remain largely unknown. Methods and Results— Here, we report that VEGF ∂/∂ mice with low vascular endothelial growth factor (VEGF) levels suffer defects in the regulation of resistance arteries. These defects are due to dysfunction and structural remodeling of the neuroeffector junction, the equivalent of a synapse between autonomic nerve endings and vascular smooth muscle cells, and to an impaired contractile smooth muscle cell phenotype. Notably, short-term delivery of a VEGF inhibitor to healthy mice also resulted in functional and structural defects of neuroeffector junctions. Conclusions— These findings uncover a novel role for VEGF in the maintenance of arterial neuroeffector function and may help us better understand how VEGF inhibitors cause vascular regulation defects in cancer patients.
- Published
- 2010
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